12-49271003-C-G

Variant names:

• chr12-49271003-C-G
• rs2335451
• NM_032704.5:c.375+1027C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032704.5(TUBA1C):​c.375+1027C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TUBA1C NM_032704.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 6 publications found

Genes affected

TUBA1C (HGNC:20768): (tubulin alpha 1c) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule cytoskeleton and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258232 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032704.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1C	NM_032704.5	MANE Select	c.375+1027C>G		intron	N/A	NP_116093.1
	TUBA1C	NM_001303114.1		c.585+1027C>G		intron	N/A	NP_001290043.1
	TUBA1C	NM_001303115.2		c.270+1027C>G		intron	N/A	NP_001290044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1C	ENST00000301072.11	TSL:1 MANE Select	c.375+1027C>G		intron	N/A	ENSP00000301072.7
	TUBA1C	ENST00000541364.5	TSL:2	c.585+1027C>G		intron	N/A	ENSP00000443475.1
	TUBA1C	ENST00000548470.1	TSL:2	n.191+1027C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.29
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2335451; hg19: chr12-49664786;